All-Atom Molecular Dynamics Simulations Reveal Significant Differences in Interaction between Antimycin and Conserved Amino Acid Residues in Bovine and Bacterial bc1 Complexes

AbstractAntimycin A is the most frequently used specific and powerful inhibitor of the mitochondrial respiratory chain. We used all-atom molecular dynamics (MD) simulations to study the dynamic aspects of the interaction of antimycin A with the Qi site of the bacterial and bovine bc1 complexes embedded in a membrane. The MD simulations revealed considerable conformational flexibility of antimycin and significant mobility of antimycin, as a whole, inside the Qi pocket. We conclude that many of the differences in antimycin binding observed in high-resolution x-ray structures may have a dynamic origin and result from fluctuations of protein and antimycin between multiple conformational states of similar energy separated by low activation barriers, as well as from the mobility of antimycin within the Qi pocket. The MD simulations also revealed a significant difference in interaction between antimycin and conserved amino acid residues in bovine and bacterial bc1 complexes. The strong hydrogen bond between antimycin and conserved Asp-228 (bovine numeration) was observed to be frequently broken in the bacterial bc1 complex and only rarely in the bovine bc1 complex. In addition, the distances between antimycin and conserved His-201 and Lys-227 were consistently larger in the bacterial bc1 complex. The observed differences could be responsible for a weaker interaction of antimycin with the bacterial bc1 complex

Complexity of hierarchical ensembles

Within the framework of generalized combinatorial approaches, complexity is determined as a disorder measure for hierarchical statistical ensembles related to Cayley trees possessing arbitrary branching and number of levels. With strengthening hierarchical coupling, the complexity is shown to increase monotonically to the limit value that grows with tree branching. In contrast to the temperature dependence of thermodynamic entropy, the complexity is reduced by the variance of hierarchical statistical ensemble if the branching exponent does not exceed the gold mean. Time dependencies are found for both the probability distribution over ensemble states and the related complexity. The latter is found explicitly for self-similar ensemble and generalized for arbitrary hierarchical trees. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/276

Post-War Ukrainа: Psychological and Psychotherapeutic Perspectives

Increased funding: one of the biggest problems facing psychologists in Ukraine is the lack of resources and funding. Increased funding for mental health services and training could help improve the quality of care that psychologists can provide to their patients. The necessary recognition of mental health and the role of psychologists in providing care can help reduce stigma and increase collaboration between psychologists and other health professionals. More resources and educational materials in Ukrainian are needed to improve access to information and resources for Ukrainian psychologists, and to support the development of a strong, locally focused research base. Creating more jobs for psychologists, especially in underserved areas, can help increase access to mental health services for those who need them. Continuous education: psychologists. Education and public awareness can help encourage more people to seek help from psychologists and other mental health professionals. Of course, these steps are only a starting point and a solution to the complex problems faced by psychologists in Ukrain

Ligand Binding and Structural Dynamics in C-Type Cytochromes

164 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 2009.The first molecular dynamic simulations of the interaction of cyt c and yeast bc1 complex are described. Contrary to results from crystallographic studies, the simulations reveal multiple dynamic hydrogen bonds and salt bridges in the cyt c-c 1 interface. A novel structural change in cyt c is also reported, involving residues 25--30, which may be responsible for cyt c destabilization. An interaction between cyt c1 monomers is proposed to be responsible for limiting the binding of cyt c to only one molecule per bc 1 dimer by altering the affinity of the cytochrome c binding site on the second cyt c1 monomer. A mechanism is also proposed explaining changes in cyt c binding affinity related to the position of the headgroup of the iron-sulfur protein.U of I OnlyRestricted to the U of I community idenfinitely during batch ingest of legacy ETD